Efficacy and Safety Study of Digital Cognitive Training and PCSK9 Inhibitor-Enhanced Lipid-lowering Strategy in Patients With Intracranial Atherosclerotic Stenosis: A 2×2 Randomized Controlled Trial

Sponsor
Peking Union Medical College Hospital
Study ID
NCT07605130
Phase
PHASE4
Status
Not Yet Recruiting

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Conditions

  • Cognitive Impairment
  • Intracranial Arteriosclerosis

Eligibility Criteria

Sex
ALL
Age
55 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Rosuvastatin — DRUG
    Rosuvastatin 20mg or Atorvastatin 40mg orally once daily, at the maximally tolerated dose, for 24 weeks. Dose may be adjusted for intolerance or safety.
  • Ezetimibe — DRUG
    Ezetimibe 10mg orally once daily, at investigator's discretion, in combination with statin therapy for 24 weeks.
  • Recaticimab — DRUG
    Recaticimab (PCSK9 inhibitor) subcutaneous injection: 150mg at week 0, 300mg at week 4, 450mg at week 12, on top of maximally tolerated statin ± ezetimibe. Total treatment duration 24 weeks.
  • Digital Cognitive Training — BEHAVIORAL
    Tablet-based adaptive cognitive training covering six domains: processing speed, attention, perception, memory, language, and executive function. Participants are instructed to train 30 minutes/day, 5 days/week for 12 weeks. The system adjusts difficulty based on performance.
  • Active Control — BEHAVIORAL
    Participants receive low-difficulty standardized tasks on the same tablet platform, with similar contact time and push frequency as the intervention group. No adaptive multi-domain training is provided. Used to control for non-specific effects of device use and attention.

Study Details

This study aims to evaluate whether digital cognitive training and/or intensive lipid-lowering therapy with a PCSK9 inhibitor can improve cognitive function in patients with intracranial atherosclerosis (ICAS). ICAS is a common cause of stroke and is also linked to thinking and memory problems. The study will enroll 420 adults aged 55-80 years who have 50-99% narrowing of an intracranial artery, subjective memory complaints, and LDL cholesterol ≥1.8 mmol/L, but who are not demented. Participants will be randomly assigned to one of four groups in a 2×2 factorial design: 1. No cognitive training + standard statin therapy 2. Cognitive training + standard statin therapy 3. No cognitive training + intensive statin plus PCSK9 inhibitor 4. Cognitive training + intensive statin plus PCSK9 inhibitor Cognitive training consists of 30 minutes of tablet-based exercises, 5 days per week for 12 weeks. The intensive lipid-lowering group receives a PCSK9 inhibitor (Recaticimab) injection at weeks 0, 4, and 12, on top of maximally tolerated statin. The main outcome is change in a composite cognitive score from baseline to 24 weeks. Secondary outcomes include changes in specific cognitive domains, MRI markers of brain structure and function, and safety measures. The study is multicenter, open-label with blinded outcome assessment, and is conducted under the approval of the ethics committee of Peking Union Medical College Hospital.

Key Dates

First listed
May 22, 2026
Start date
May 25, 2026
Status verified
May 2026
Primary completion
Sep 30, 2028
Completion
Jul 31, 2029

Study Design

Enrollment
420 participants (estimated)
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Control group
    No digital cognitive training + maximum statin tolerance only Participants receive maximally tolerated statin (rosuvastatin 20mg or atorvastatin 40mg daily, with optional ezetimibe 10mg at investigator discretion) for 24 weeks. No digital cognitive training. Instead, they receive low-difficulty standardized tasks as active control (same tablet, contact time, and push frequency but no adaptive multi-domain training).
  • Experimental: Lipid-lowering intervention group
    No digital cognitive training + maximum tolerance statin plus PCSK9 inhibitor Participants receive maximally tolerated statin (as in Arm 1) plus subcutaneous PCSK9 inhibitor (Recaticimab) injections: 150mg at week 0, 300mg at week 4, 450mg at week 12. No digital cognitive training; they receive the same low-difficulty active control as in Arm 1. Total treatment duration is 24 weeks.
  • Experimental: Training intervention group
    Digital cognitive training + maximum statin tolerance only Participants receive maximally tolerated statin (as in Arm 1) for 24 weeks. In addition, they undergo 12 weeks of digital cognitive training: adaptive, multi-domain (processing speed, attention, perception, memory, language, executive function) delivered via tablet. Participants are asked to train 30 minutes/day, 5 days/week. Minimum dose: ≥3 days/week and ≥20 minutes/session or ≥60 minutes/week.
  • Experimental: Combined intervention group
    Digital cognitive training + maximum tolerance statin plus PCSK9 inhibitor Participants receive both intensive interventions: maximally tolerated statin plus PCSK9 inhibitor (Recaticimab injections at weeks 0,4,12 as in Arm 3) \*\*and\*\* 12 weeks of digital cognitive training (same adaptive program as in Arm 2). Total treatment duration is 24 weeks.

Primary Outcome Measure

Change from baseline in composite cognitive Z-score at week 24 [ Time Frame: Baseline to 24 weeks ]

Central Contacts

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